Retinoblastoma resource: Researchers create a more accurate research model
St. Jude Department of Oncology created retinoblastoma models that more closely mimic the biology of patient tumors. St. Jude Children’s Research Hospital has created a laboratory model for studying retinoblastoma driven by inherited mutations in the RB1 gene. This disease is a rare cancer of the retina, impacting the thin tissue inside the back of the eye. The researchers created retinoblastoma organoid models that closely mimic the biology of tumors in patients.
This disease occurs in very young children, and in some cases, children are born with the disease. “What we have developed with these retinoblastoma organoids is, for the first time ever, a laboratory model where it’s possible to study the processes that go on when retinoblastoma is starting to form,” said co-corresponding author Michael Dyer, Ph.D., St. Jude Department of Developmental Neurobiology chair.
The need for a new model
Retinoblastoma models, including cell lines, genetically engineered mouse models, and patient-derived xenografts, have been useful for research. Jude research has shown that mouse models for retinoblastoma are not always reliable predictors for preclinical drug development studies. “Understanding what else drives tumor development, beyond RB1, could uncover new targets for therapy, impact disease treatment and possibly stop new tumors from forming,” said co-corresponding author Rachel Brennan, M.D., St. Jude Department of Oncology.”If we uncover the mystery of what leads some patients to develop second tumors later in life, we can develop more effective screening programs and early interventions to save lives”.
Brennan co-leads the retinoblastoma clinical program with ocular oncologist Matthew Wilson, M.D., University of Tennessee Health Sciences Center, who is also a co-author of the paper.
A better way to study the disease
The cells were created using samples from retinoblastoma patients who had germline mutations in RB1. The cells from the organoids were injected into mice, where tumors eventually formed. The researchers conducted whole-genome sequencing, RNA sequencing, and methylation analysis of these retinoblastoma tumors and found that they were indistinguishable from patient samples. “The ability of the organoid models to do so is unique because cell lines with RB1 mutations do not spontaneously develop into retinoblastoma tumors.”
Authors and Funding
The study was funded by the National Institutes of Health, the Shipley Foundation, Alex’s Lemonade Stand Foundation, and ALSAC, the fundraising and awareness organization of St. Jude.
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